P1509: CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND PREVIOUS INFECTIONS HAD IMPACT ON INFECTIOUS COMPLICATIONS IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA TREATED WITH VENETOCLAX: A MULTICENTRE SEIFEM STUDY
Authors: Francesco Autore, Andrea Visentin, Marina Deodato, Candida Vitale, Eugenio Galli, Alberto Fresa, Rita Fazzi, Alessandro Sanna, Jacopo Olivieri, Ilaria Scortechini, Maria Ilaria DEL Principe, Paolo Sportoletti, Luana Schiattone, Nilla Maschio, Davide Facchinelli, Marta Coscia, Alessandra Tedeschi, Livio Trentin, Idanna Innocenti, Anna Candoni, Alessandro Busca, Livio Pagano, Luca Laurenti
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Infections are a major source of morbidity and mortality in patients with Chronic Lymphocytic Leukemia (CLL). The development of targeted agents decreased the rate of these complications in comparison to standard chemoimmunotherapy regimens. However, these patients often elderly, with other comorbidities, heavily treated, experienced serious infections. Aims: The aim of our study was to evaluate the incidence of clinically or microbiologically documented bacterial, fungal and viral infectious complications in CLL patients treated with venetoclax. Methods: The retrospective multicenter study included CLL patients treated since 2017 with venetoclax single agent until progression or toxicity or venetoclax plus antiCD20 antibody (mainly rituximab as part of VR protocol for 24 months). Results: The analysis was conducted on 287 CLL patients treated in 16 different institutions: 151 patients were treated with venetoclax and 136 patients were treated with venetoclax plus antiCD20 antibody. The median number of prior treatment regimens was 2 in the first group and 1 in the second. Patients of the first group were older, more frequently had del17/TP53mut, renal impairment (CrCl <70) and lower basal levels of IgG. We recorded 181 events of infections grade 1-2, occurred in 114 patients (out of 287, 40%): the most common infections involved the respiratory tract (106 events), followed by genitourinary tract (23) and gastrointestinal one (16). Pathogens implicated in the infections were isolated only in 57 cases (36 viral, 18 bacterial and 3 fungal). We recorded 103 episodes of infections grade 3-4, occurred in 73 patients (out of 287, 25%): the most common infections involved the respiratory tract (71 events), followed by sepsis (13) and gastrointestinal tract (7 events). Pathogens implicated in the infections were isolated in 64 cases (40 viral, 21 bacterial and 3 fungal). When comparing time of first infection of any grade between the patients treated with venetoclax and those treated with venetoclax plus antiCD20 antibody, we registered a trend toward a higher rate of infection in the latter group after the first year (p=0.066). This difference was not confirmed when we focused on grade 3-4 infections. Risk factors for infection in the whole population in univariate analysis were Chronic obstructive pulmonary disease (COPD), CrCl<70, stage A, prior treatments, infections in the previous 12 months before venetoclax treatment; in multivariate resulted COPD (OR 5.39) and previous infections in the last 12 months (OR 2.57). Stratifying patients according to COPD and previous infections in the last 12 months we obtained 3 groups significantly different in terms of risk for infections (p <0.001; figure 1). The cumulative incidence of infection was 69% in the first year if patient showed both COPD and at least an infection in the previous 12 months. If considering only grade 3-4 infections, risk factors significant in the univariate analysis were smoke, previous infections and COPD. Only COPD was the unique significant variable in multivariate analysis (OR 2.62). Treatment was withdrawn in 80 cases, of whom 22 definitive. Patients were hospitalized in 68 cases. We recorded 83 deaths and the median OS was 55 months. The main causes of death were CLL progression in 36 cases and infections in 22 cases. Summary/Conclusion: We recorded a significant rate of infections, most of grade 1-2; we found a role of comorbidities such as COPD and previous infections as risk factors; COPD resulted a risk factor also for infections of grade 3-4.Keywords: Infection, Venetoclax, B-CLL